Summary 1) Current data on prevalence and trends for pulmonary nontuberculous mycobacteria disease for the United States are fragmentary. While recent reports suggest rising numbers, he last population-based prevalence data were published more than twenty years ago. The availability of large-linked datasets for integrated health care systems allows analysis of prevalence and trends in large populations over extended time periods. We abstracted mycobacterial culture results from electronic laboratory databases and linked to other datasets containing clinical and demographic information. Possible cases were defined as a single positive NTM pulmonary isolate, and definite cases were defined as two positive sputum cultures, or one positive culture from a bronchoalveolar lavage or lung biopsy. Annual prevalence was calculated using US census data;average annual prevalence is presented for 2004-2006. Poisson regression models were used to estimate the annual percent change in prevalence. Overall, 28,697 samples from 7940 patients were included in the analysis. Of these, 3988 (50%) were defined as possible cases, and 1865 (47%) of these were defined as definite cases. Average annual (2004-2006) site-specific prevalence ranged from 1.4 to 6.6 per 100,000. Prevalence was 1.l to 1.6 fold higher among women relative to men across sites. The prevalence of NTM lung disease was increasing significantly at the two sites where trends were studied, by 2.6% per year among women and 2.9% per year among men. Among persons aged >60 years, annual prevalence increased from 19.6 / 100,000 during 1994-1996 to 26.7/100,000 during 2004-2006. The epidemiology of mycobacterial disease in the United States has changed over the last 20 years, with a decline in pulmonary tuberculosis and an increase identified in pulmonary nontuberculosis mycobacterial disease. These findings highlight the increased burden among women and older adults, and the need for regular evaluation and monitoring of patients with this condition. 2) Based on geographic differences in NTM prevalence identified, we became interested in further understanding the geographic variability of NTM lung disease and possible gene-environment interactions. The ubiquitous prevalence of the NTM organisms and the rarity of NTM disease support the role for a genetic susceptibility to disease from these organisms. A previously conducted multi-site study of NTM prevalence among persons with Cystic Fibrosis, a high risk population, identified geographic variability in NTM which was correlated with ambient water vapor content. This finding is supported by environmental microbiologic and laboratory studies of NTM. We analyzed data from a nested case-control study conducted as part of this multisite study to identify the potential risk of individual exposures for NTM infection. None of the common exposures such as bathing, showering, or drinking water were associated with infection. We hypothesize that individual genetic susceptibility and environmental factors such as temperature, humidity, and drinking water source are more important predictors of disease than individual behaviors. We are continuing our work on analyzing the environmental factors associated with NTM through mapping NTM cases identified through the Medicare (CMS) and correlating with available environmental data. 3) Bronchiectasis is a condition characterized by permanent bronchial dilation and repeated infections, particularly with mycobacteria. The Laboratory of Clinical Infectious Diseases, NIAID, is currently conducting clinical studies of bronchiectasis natural history. However, data on the prevalence and trends of bronchiectasis are lacking. Prevalence and trend estimates are needed to describe the burden of disease and improve public health resource allocation. We analyzed a 5% sample of Medicare Carrier claims database to assess the prevalence and trends for bronchiectasis among Medicare beneficiaries from 2000-2006. The Medicare Carrier claims database comprises billing claims submitted by non-institutional care providers. Records were extracted for beneficiaries who had at least one ICD-9-CM claim diagnosis code of acquired bronchiectasis (494, 494.1 or 494.0) in a single year. The average annual prevalence from 2000-2006 was 322 per 100,000 population for women and 214 per 100,000 population for men, for a 50% increased prevalence among women relative to men. The trend in annual prevalence was increasing among both men and women. Based on the prevalence for 2006, we estimated a total of 88,333 cases among women and 42,704 cases among men for the population aged 65 years in that year. We identified a high and increasing burden of bronchiectasis diagnosed and managed in the outpatient setting among persons aged >=65 years from 2000-2006. These findings support previous studies showing a higher prevalence in women and among older individuals. 4) We also estimated the trends and burden of bronchiectasis-associated hospitalizations in the United States using hospital discharge records. We extracted hospital discharge records containing ICD-9-CM codes for bronchiectasis (494, 494.0, and 494.1) as any discharge diagnosis from the State Inpatient Databases from the Agency for Healthcare Research and Quality. Discharge records were extracted for 12 states with complete and continuous reporting from 1993 to 2006. The average annual age-adjusted hospitalization rate from 1993 to 2006 was 16.5 hospitalizations per 100,000 population. From 1993 to 2006 the age-adjusted rate increased significantly with an average annual percent increase of 2.4% among men and 3.0% among women. Women and persons aged >60 years had the highest rate of bronchiectasis-associated hospitalizations. The median cost for inpatient care was 7,827 USD (range: 13-543914). The average annual age-adjusted rate of bronchiectasis-associated hospitalizations increased from 1993 to 2006.